Pediatr Infect Vaccine.  2017 Dec;24(3):152-159. 10.14776/piv.2017.24.3.152.

Clinical Manifestations and Treatment in Korean Patients with X-Linked Agammaglobulinemia

• Cho H
• Kim JG

• KMID: 2401390
• DOI: http://doi.org/10.14776/piv.2017.24.3.152

Abstract

PURPOSE
X-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by mutations in the Bruton's tyrosine kinase (Btk) gene. The aim of this study was to investigate the clinical manifestations, molecular features, and treatment status of XLA in Korean patients at Seoul National University Children's Hospital.
METHODS
Fourteen Korean boys with XLA showing serum agammaglobulinemia, non-detectable to less than 2% of peripheral B-cells, and mutation of the Btk gene were enrolled. We observed the clinical features, laboratory findings, status of treatment, and complications in these XLA patients.
RESULTS
All XLA patients had a history of recurrent bacterial infections before diagnosis, and 20% of them had a neutropenia. Of the XLA patients 35.7% had a family history of XLA and 75% of their mothers were carriers. Btk gene analysis showed variable gene mutations in Xq22 including 9 amino acid substitutions, 3 frameshifts, 1 premature stop codon, and 1 splice defect. After intravenous immunoglobulin replacement therapy, infection episodes decreased, but complications such as bronchiectasis and chronic sinusitis remained.
CONCLUSIONS
In patients less than 4 years of age with recurrent infection, analysis of serum gamma globulin levels and the Btk gene are recommended for the early diagnosis of XLA and for the appropriate prevention of recurrent infection.

Keyword

Bruton type agammaglobulinemia; Immunoglobulins, intravenous

MeSH Terms

Agammaglobulinemia*
Amino Acid Substitution
B-Lymphocytes
Bacterial Infections
Bronchiectasis
Codon, Nonsense
Diagnosis
Early Diagnosis
gamma-Globulins
Humans
Immunoglobulins
Immunoglobulins, Intravenous
Mothers
Neutropenia
Protein-Tyrosine Kinases
Seoul
Sinusitis
Codon, Nonsense
Immunoglobulins
Immunoglobulins, Intravenous
Protein-Tyrosine Kinases
gamma-Globulins

Figure

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  Fig. 1 Age at diagnosis in 14 patients with X-linked agammaglobulinemia.

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  Fig. 2 Bruton tyrosine kinase gene study in patient #2, his mother and sister. The mutation type was splice defect and his mother and sister were carriers.

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  Fig. 3 Mutation sites of Bruton's tyrosine kinase (Btk) gene in 14 patients with X-linked agammaglobulinemia. Abbreviation: UTR, untranslated region.

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